Measurement of mesothelioma on thoracic CT scans: a comparison of manual and computer-assisted techniques

Our purpose in this study was to evaluate the variability of manual mesothelioma tumor thickness measurements in computed tomography (CT) scans and to assess the relative performance of six computerized measurement algorithms. The CT scans of 22 patients with malignant pleural mesothelioma were collected. In each scan, an initial observer identified up to three sites in each of three CT sections at which tumor thickness measurements were to be made. At each site, five observers manually measured tumor thickness through a computer interface. Three observers repeated these measurements during three separate sessions. Inter- and intra-observer variability in the manual measurement of tumor thickness was assessed. Six automated measurement algorithms were developed based on the geometric relationship between a specified measurement site and the automatically extracted lung regions. Computer-generated measurements were compared with manual measurements. The tumor thickness measurements of different observers were highly correlated (r > or = 0.99); however, the 95% limits of agreement for relative inter-observer difference spanned a range of 30%. Tumor thickness measurements generated by the computer algorithms also correlated highly with the average of observer measurements (r > or = 0.93). We have developed computerized techniques for the measurement of mesothelioma tumor thickness in CT scans. These techniques achieved varying levels of agreement with measurements made by human observers.     

Five year study of prenatal testing for Huntington''s disease: demand, attitudes, and psychological assessment.

Adult predictive and prenatal testing programmes for Huntington's disease (HD) in Canada have been available since 1986. However, the demand for prenatal testing and the reasons why some people choose not to have the prenatal test for this late onset disorder have not been well documented. In addition, the knowledge and attitudes of adult predictive testing candidates and their partners about prenatal testing are not well known nor are the psychological effects of prenatal testing well understood. As of September 1991, 425 subjects had entered the Canadian Collaborative Study of Predictive Testing and, of these, 47 subjects or their partners had become pregnant. Of this group, 14 (30%) couples requested prenatal testing, 24 (51%) couples did not want prenatal testing, and nine (19%) at risk subjects had already received a decreased risk through adult predictive testing and, therefore, were not eligible for the prenatal test. Of the 14 couples who initially requested prenatal testing, seven withdrew. Thus, demand for the prenatal test by eligible candidates was 7/38 or 18%, which is much lower than the 32 to 65% expected based on early survey data. The most frequently cited reason for declining prenatal testing was the hope that a cure would be found in time for their children. While the majority of adult predictive testing candidates (71%) in our study had accurate information about definitive prenatal testing, many (63%) did not have a correct understanding of exclusion prenatal testing. Although no serious adverse events such as suicide planning or admission to psychiatric hospital have occurred, a particular need for careful counselling was identified for those at risk candidates and their partners who have one prenatal test and feel compelled to use the test again in future pregnancies. Even though prenatal testing for HD is not requested as often originally expected, it still remains a desired option for some at risk persons and their partners.     

Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin

To assess the risk of miscarriage after in-vitro fertilization(IVF) with respect to age, cause of infertility, ovarian morphologyand treatment regimen, a retrospective analysis was performedof the first 1060 pregnancies conceived between June 1984 andJuly 1990 as a result of 7623 IVF cycles. Superovulation inductionwas achieved with human menopausal gonadotrophin (HMG) and/orpurified follicle stimulating hormone (FSH) together with eitherclomiphene citrate or the gonadotrophin hormone-releasing hormone(GnRH) agonist buserelin, the latter either as a short ‘flare’regimen or as a ‘long’ regimen to induce pituitarydesensitization. There were 282 spontaneous abortions (26.6%)and 54 ectopic pregnancies (5.1%). The mean age of women withongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2(SD 4.1) years in those who miscarried, which were significantlydifferent (P = 0.008). There was no relation between the miscarriagerate and the indication for IVF. The miscarriage rate was 23.6%in women with normal ovaries compared with 35.8% in those withpolycystic ovaries [P = 0.0038, 95% confidence interval (CI)4.68–23.10%]. There was no difference in the miscarriagerate between treatment with HMG or FSH. Women whose ovarieswere normal on ultrasound were just as likely to miscarry ifthey were treated with clomiphene or with the long buserelinprotocol. Those with polycystic ovaries, however, had a significantreduction in the rate of miscarriage when treated with the longbuserelin protocol, 20.3% (15/74), compared with clomiphenecitrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82–40.09%).     

Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe

Escherichia coli O15:K52:H1 is a significant extraintestinal pathogen in Europe (G. Prats et al., J. Clin. Microbiol. 38:201-209, 2000). To search for evidence of this clonal group outside of Europe, 75 non-European E. coli isolates of serogroup O15 were compared with five members of the O15:K52:H1 clonal group from Barcelona, Spain, according to genomic background, virulence genotypes, and antimicrobial resistance profiles. Amplification phylotyping showed that 16 (21%) of the 75 non-European O15 isolates corresponded with the O15:K52:H1 clonal group. The 16 non-European O15:K52:H1 clonal group members represented diverse geographic locales. They were isolated almost exclusively from humans with extraintestinal infections and accounted for 50% of all O15 isolates from five human clinical collections studied. Most non-European clonal group members exhibited a consensus virulence factor profile that included the F16 or F7-2 papA alleles (P fimbrial structural subunit), papG allele II (P fimbrial adhesin), iha (putative adhesin siderophore), and iutA (aerobactin receptor). This resembles the virulence profiles of (i) European representatives of the O15:K52:H1 clonal group and (ii) phylogenetically related "clonal group A," a recently recognized significant contributor to trimethoprim-sulfamethoxazole resistance in the United States (A. R. Manges et al., N. Engl. J. Med. 345:1007-1013, 2001). Antimicrobial resistance profiles were variable, and resistance was inconsistently transferred by conjugation. These findings indicate that the O15:K52:H1 clonal group is broadly distributed beyond Europe, exhibits previously unrecognized phenotypic and genotypic diversity, and contributes significantly to extraintestinal infections in humans.     

A controlled study comparing patients with and without polycystic ovaries undergoing in-vitro fertilization

The outcome of in-vitro fertilization and embryo transfer (IVF—ET)was compared in 76 patients with polycystic ovaries (PCO) diagnosedon pre-treatment ultrasound scan, and 76 control patients whohad normal ovaries and were matched for age, cause of infertilityand stimulation regimen. Despite receiving significantly lesshuman menopausal gonadotrophin (HMG), patients with PCO, ascompared with controls, had significantly higher serum oestradiollevels on the day of human chronic gonadotrophin administration(5940 ± 255 versus 4370 ± 240 pmol/1, P < 0.001),developed more follicles (14.9 ± 0.7 versus 9.8 ±0.6, P < 0.001) and produced more oocytes (9.3 ± 0.6versus 6.8 ± 0.5, P = 0.003). However, fertilizationrates were reduced in the PCO patients (52.8 ± 3.4% versus66.1 ± 3.4%, P = 0.007). There was no significant differencein cleavage rates. The pregnancy rate/embryo transfer was 25.4%in the PCO group and 23.0% in the group with normal ovaries.There were three high order multiple pregnancies in the PCOgroup compared with none in the group with normal ovaries. Ofthe PCO patients, 10.5% developed moderate/severe ovarian hyperstimulationsyndrome (OHSS) compared with none of the controls (P = 0.006).Patients with and without PCO undergoing IVF have comparablepregnancy and livebirth rates. However, it is important to diagnosePCO before ovarian stimulation is initiated as these patientsare more likely to develop moderate or severe OHSS following1VF—ET.     

Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia

Human immunodeficiency virus type 1 (HIV-1) infection often results in disorders of the central nervous system, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNFalpha) released by activated and/or infected macrophages/microglia plays a role in the process of neuronal damage seen in AIDS patients. In light of earlier studies showing that the activation of the insulin-like growth factor I receptor (IGF-IR) exerts a strong neuroprotective effect, we investigated the ability of IGF-I to protect neuronal cells from HIV-infected macrophages. Our results demonstrate that the conditioned medium from HIV-1-infected macrophages, HIV/CM, causes loss of neuronal processes in differentiated PC12 and P19 neurons and that these neurodegenerative effects are associated with the presence of TNFalpha. Furthermore, we demonstrate that IGF-I rescues differentiated neurons from both HIV/CM and TNFalpha-induced damage and that IGF-I-mediated neuroprotection is strongly enhanced by overexpression of the wt IGF-IR cDNA and attenuated by the antisense IGF-IR cDNA. Finally, IGF-I-mediated antiapoptotic pathways are continuously functional in differentiated neurons exposed to HIV/CM and are likely supported by TNFalpha-mediated phosphorylation of I(kappa)B. All together these results suggest that the balance between TNFalpha and IGF-IR signaling pathways may control the extent of neuronal injury in this HIV-related experimental setting.